异黄酮哌嗪衍生物的合成

异黄酮类化合物广泛存在于植物中 ,具有多种生理活性 .以苯乙酸和间苯二酚为原料 ,合成了 9个异黄酮哌嗪衍生物 ,均未见文献报道 .其结构经过IR ,MS和1H NMR确证 .     

雌激素哌嗪类衍生物的合成及其促骨生长活性

设计合成了以籍次乙基为桥将雌激素通过 3 OH醚化与 4种不同哌嗪环相连的衍生物 ,包括中间体共合成了 12个化合物 ,其中 8个目标物及 3个中间体未见文献报道 .结构经质谱、核磁共振谱、红外光谱及元素分析确定 .同时测定了目标物对体外培养小鼠胚胎长骨生长的影响 ,结果显示由雌酚酮和雌二醇与不同的哌嗪环相连所得到的衍生物抑制骨吸收、促进骨形成的作用均不低于相应的母体雌激素 .表明哌嗪环的引入不影响雌激素对骨的药理作用 ,所合成的 4种化合物可以作为骨靶向雌激素的弹头 ,进一步与骨靶向载体连接 .     

哌嗪取代二氢吡啶新衍生物的合成及其钙拮抗活性研究

设计合成了5个哌嗪取代二氢吡啶新衍生物，并用^45Ca跨膜内流动测定方法研究了目标物对大鼠主动脉电压依赖性钙离子通道（PDC）Ca^2 内流的影响。结果显示5个化合物对PDC的阻滞作用强于阳性对照物硝苯吡啶，表明它们均具有较强的钙拮抗活性，值得进一步进行药理研究。     

羟丙哌嗪衍生物的合成及其镇咳活性

目的寻找具有更强镇咳活性的化合物.方法以苯胺和二乙醇胺为原料,通过环合反应制得苯基哌嗪(2),2与环氧氯丙烷发生N-烷基化反应,所得产物和胺直接开环制得羟丙哌嗪衍生物;用"序贯法"测试目标化合物对小鼠的镇咳活性.结果与结论合成了15个未见报道的新化合物,并通过核磁共振氢谱、质谱确证结构;小鼠试验表明,所有新化合物均具有显著的镇咳效果,与阳性对照--左羟丙哌嗪(LD)的镇咳活性相当.     

β-榄香烯取代哌嗪酰胺类衍生物的合成及抗肿瘤活性研究

目的设计合成β-榄香烯取代哌嗪酰胺类衍生物并进行体外抗癌活性筛选。方法通过合成β-榄香烯单氯代物,在其结构中引入取代哌嗪结构来合成β-榄香烯取代哌嗪衍生物,然后再与取代苯甲酰氯或取代苯丙烯酰氯反应制得β-榄香烯取代哌嗪酰胺类衍生物。采用MTT法测定了目标化合物对人宫颈癌细胞、人肝癌细胞、人纤维肉瘤细胞等10种细胞的增殖抑制作用。结果与结论合成了23个未见文献报道的β-榄香烯取代哌嗪酰胺类衍生物。经1H—NMR、MS波谱分析确证结构。其中21个化合物经MTT法测定了体外抗肿瘤活性,结果显示活性大多高于β-槛香烯。     

苄基哌嗪类衍生物的合成与蛋白酪氨酸激酶抑制活性的研究

目的合成苄基哌嗪类衍生物,考察目标化合物对蛋白酪氨酸激酶(PTK)的抑制活性。方法用呋喃甲醛和丙二酸合成呋喃丙烯酸,以15种取代苄基哌嗪为原料,分别与呋喃丙烯酸反应得到目标化合物。采用酶联免疫吸附法(Elisa)测定所得化合物对PTK的抑制活性,并计算抑制率,筛选出具有抑制PTK活性的化合物。结果所得化合物均对PTK有一定的抑制活性。结论通过优化反应条件,成功合成15种苄基哌嗪类化合物,原料廉价易得,合成方法简单,反应温和。化合物结构经IR、~1H NMR、EA和MS确证。经初步活性筛选发现化合物2h和2k的抑制活性较强。     

哌嗪生产与衍生物开发应用

哌嗪无色澄清状液体，有类似氨的味道，危险货物编号：32106；联合国编号：2579；国际海运危规页码(IMDG CODE)：8211，其蒸汽与空气形成爆炸混合物，遇见明火、高热能引起燃烧爆炸，其蒸汽比空气密度大，能在较低处扩散到相当远地方。储存在阴凉通风仓间内，远离火种和热源，     

哌嗪衍生物的合成及其正性肌力作用的初步研究

合成了两个系列共８个哌嗪类衍生物，用红外、核磁、质谱及元素分析确证结构。经豚鼠离体心房正性肌力作用试验，所筛选的８个体例物中，有７个具有不同程度的活性。其中目标物Ⅱ与Ⅸ正性肌力作用均强于对照品氨力农及维司力农（ｖｅｓｎａｒｉｎｏｎｅ），且（Ⅸ）与氨力农比较有显著性差异。     

芳烷酮哌嗪衍生物的设计合成及镇痛活性

以中枢兴奋性氨基酸NMDA受体多胺调节位点为靶点，设计合成芳烷酮哌嗪类全新化合物并研究它们的镇痛活性。哌嗪经甲酰基保护后，与相应的卤代芳烃进行烷基化反应，制备目标化合物。以小鼠扭体法、大鼠热板法、大鼠光热甩尾法等动物体内镇痛模型测试目标化合物的镇痛活性。共合成64个未见文献报道的新化合物，其结构经质谱、核磁共振谱及元素分析确证。镇痛药理试验显示：该类化合物具有较好的镇痛作用及作为新型非阿片类镇痛药开发的潜在价值。化合物I₁₂，I₁₄，I₂₁和I₃₇在三种镇痛模型上均显示很强的镇痛活性，具有深入研究的价值。     

哌嗪衍生物的不同合成策略

哌嗪环是许多上市药物结构中的重要组成部分,在药物设计中有重要作用。本文首次以不同策略合成了两个含哌嗪的化合物。对于其中一个目标物,通过具有高反应活性的异硫氰酸酯中间体来构建哌嗪硫代酰胺结构。另一目标化合物通过傅克酰化、偶联反应和麦克加成构建。两条合成路线均有步骤短、产率高的优点,可为类似含哌嗪化合物的合成提供参考。     

Synthesis and calcium antagonistic activity of some new 2-thioxo-1,2,3,4-tetrahydropyrimidine derivatives.

A series of 1,2,3,4-tetrahydro-6-methyl-4-(substituted phenyl)-2-thioxo-5-pyrimidinecarboxylic acid methyl esters were synthesized by condensing thiourea with methyl acetoacetate and nonsubstituted or differently substituted benzaldehydes in absol. ethanol using HCl as a catalyst according to the Biginelli reaction. The structures of the compounds were confirmed by elemental and spectroscopic analysis. -The compounds were evaluated for their calcium antagonistic activity on the basis of their potency in inhibiting [3H] PN 200-110 binding on microsomes obtained from rat skeletal muscle.     

Synthesis, QSAR and calcium channel modulator activity of new hexahydroquinoline derivatives containing nitroimidazole

The discovery that 1,4-dihydropyridine class of calcium channel antagonists inhibit Ca2+ influx represented a major therapeutic advance in the treatment of cardiovascular disease. In contrast to the effects of known calcium channel blockers of the Nifedipine-type, the so-called calcium channel agonists, such as Bay K8644 and CGP 28392, increase calcium influx by binding at the same receptor regions. Our goal was to discover a dual cardioselective Ca2+-channel agonist/vascular selective smooth muscle Ca2+ channel antagonist third-generation 1,4-dihydropyridine drug which would have a suitable therapeutic profile for treating congestive heart failure (CHF) patients. A series of unsymmetrical alkyl, cycloalkyl and aryl ester analogues of 2-methyl-4-(1-methyl)-5-nitro-2-imidazolyl-5-oxo-1,4,5,6,7, 8-hexahydroquinolin-3-arboxylate were synthesized using modified Hantzsch reaction. All compounds show calcium antagonist activity on guinea-pig ileum longitudinal smooth muscle and some of them show agonist effect activity on guinea-pig auricle. Effect of structural parameters on the Ca2+ channel agonist/antagonist was evaluated by quantitative structure-activity relationship analysis. These compounds could be considered as a synthon for developing a suitable drug for treating CHF patients.     

Pharmacological properties and SAR of new 1,4-disubstituted piperazine derivatives with hypnotic-sedative activity

Preparation, pharmacological properties and structure-activity relationships of new pyrimidyl-piperazine derivatives, exhibiting sedative and hypnotic activity in mice, are reported. The hypnotic activity of the compounds was comparable with that of zopiclone (the known hypnotic-sedative agent), their interaction with ethanol, however, being much lower. The obtained results suggested that zopiclone and pyrimidylpiperazines 2, 4 and 5 exerted their pharmacological activity through a different mechanism - zopiclone through the interaction with benzodiazepine receptors and compounds 2, 4 and 5 through an unidentified molecular target. The pharmacological properties of compound 3 could be the result of a mixed mechanism of action, combining the properties of zopiclone and those of compounds 2, 4 and 5. A common feature of zopiclone and compounds 2 and 3 was that, after their systemic administration, independently of mechanism of action, together with the hypnotic effect a reduction of the 5-HT turnover in the mouse brain was observed. Minimum structural requirements for the hypnotic activity were formulated. Structural considerations have shown that removing the alpha-carbonyl group did not influence the drug's ability to inhibit the locomotor activity. However, it did influence its ability to disturb motor coordination or abolish the righting reflex within non-lethal doses.     

Synthesis and calcium channel antagonist activity of new 1,4-dihydropyridine derivatives containing dichloroimidazolyl substituents

A group of dialkyl, dicycloalkyl and diaryl ester analogues of nifedipine (CAS 21829-25-4), in which the ortho-nitrophenyl group at position 4 is replaced by a 4,5-dichloroimidazolyl substituent, were synthesized and evaluated as calcium channel antagonists using the high K+ contraction of guinea-pig ileal longitudinal smooth muscle. The results for the symmetrical esters in alkyl esters series showed that increasing the length of the methylene chain in C3 and C5 ester substituents (from n = 0 to n = 2) increased the activity. When increasing of the length was accompanied by increase of the hindrance, the activity decreased. In the unsymmetrical diester series, the results showed when R1 is a small substituent (R1 = Me), increasing of the lipophilic property in R2 substituent increases the activity if this high lipophilicity is not accompanied by steric hindrance. The results demonstrate that in the unsymmetrical series, several compounds (benzyl methyl, benzyl isopropyl and cyclohexyl ethyl) had activity similar to that of the reference drug nifedipine. In symmetrical diesters compounds, the most active compound was the diphenethyl ester derivative being more active than nifedipine. These structure-activity data indicate that the 4-(4,5-dichloroimidazolyl) moiety is the bioisoester of 3-nitrophenyl and 2,3-dichlorophenyl moieties.